Antioxidant-containing polymer compositions lose their efficiency of cross-linking when subjected to ionizing radiation because of the free radical protective activity of the antioxidant. For certain applications, such as medical applications like load bearing polymers, cross-linking is beneficial to reduce the wear rate of the polymer. Radiation cross-linking has been shown to reduce the wear rate of polymeric material and thus extend the longevity of total joint reconstructions. However, residual free radicals created by radiation compromise the long-term oxidative stability of the polymer. Therefore, it is crucial to either eliminate or stabilize the free radicals so that deleterious oxidation is avoided or minimized. One method of free radical elimination through irradiation and melting were described by Merrill et al. (see U.S. Pat. No. 5,879,400). This is an acceptable method; however, such a melt history also reduces the crystallinity of the polyethylene and thus affects its mechanical and fatigue properties (see Oral et al., Biomaterials, 27:917-925 (2006)).
Other methods that avoid melting after irradiation is the one described, among other things, by Muratoglu and Spiegelberg (see US 2004/0156879). These methods use an antioxidant, such as α-tocopherol, to stabilize the free radicals in irradiated polymeric material and prevent long-term oxidation. According to certain embodiments of these methods, α-tocopherol can be incorporated into polymeric material after irradiation through contact and diffusion.
α-Tocopherol can be used to lessen or eliminate reactivity of the residual free radicals in irradiated UHMWPE to prevent oxidation. The incorporation of α-tocopherol into irradiated UHMWPE can be achieved through either blending α-tocopherol with the UHMWPE powder prior to consolidation or diffusing the α-tocopherol into UHMWPE after consolidation of powder, both of which are taught in U.S. application Ser. No. 10/757,551 (US 2004/0156879). The latter also can be performed after the consolidated UHMWPE is irradiated. Since radiation cross-links the UHMWPE and thus increases its wear resistance, it can be beneficial to irradiate the consolidated UHMWPE in its virgin state without any α-tocopherol present. On the other hand, cross-linking and melting has been shown to decrease certain mechanical properties and fatigue resistance of UHMWPE (see Oral et al., Mechanisms of decrease in fatigue crack propagation resistance in irradiated and melted UHMWPE, Biomaterials, 27 (2006) 917-925). Wear of UHMWPE in joint arthroplasty is a surface phenomenon whereas fatigue crack propagation resistance is largely a property of the bulk. Therefore, UHMWPE with high cross-linking on the surface and less cross-linking in the bulk can be beneficial as an alternate bearing in joint arthroplasty. Oral et al. (Characterization of irradiated blends of α-tocopherol and UHMWPE, Biomaterials, 26 (2005) 6657-6663) have shown that when present in UHMWPE, α-tocopherol reduces the efficiency of cross-linking of the polymer during irradiation. Muratoglu et al. (see US 2004/0156879) described, among other things, high temperature doping and/or annealing steps to increase the depth of penetration of α-tocopherol into irradiated UHMWPE. Muratoglu et al. (see U.S. application Ser. No. 11/465,544, filed Aug. 18, 2006; PCT/US2006/032329 Published as WO 2007/024689) described, among other things, annealing in supercritical carbon dioxide to increase depth of penetration of α-tocopherol into irradiated UHMWPE. UHMWPE medical implants can have a thickness of up to 30 mm and sometimes larger. Penetrating such large implants with α-tocopherol by diffusion can take a long time, however. Also it is preferable in some embodiments to diffuse α-tocopherol into an irradiated UHMWPE preform and subsequently machine that preform to obtain the finished implant. The preform has to be larger than the implant and therefore the diffusion path for α-tocopherol is increased.
In order to eliminate free radicals, several further methods can be used such as melting (see, e.g., Muratoglu et al. US 2004/0156879), mechanical deformation and recovery (see, e.g., Muratoglu et al., US 2005/0124718) or high pressure crystallization (see, e.g., Muratoglu et al. U.S. application Ser. No. 10/597,652; PCT/US05/003305 published as WO 2005/074619), which are incorporated herein by reference.
Post-irradiation melting also has been advanced as a method of eliminating the free radicals. This method has been successful without compromising the oxidative stability of the polymer, but reduces the crystallinity and in turn certain mechanical properties of the polymer. For certain human joint applications and certain high-stress designs, a decrease in certain mechanical properties is to be avoided. Alternative approaches to post-irradiating melting also have been developed. For instance, post-irradiation mechanical deformation or post-irradiation antioxidant diffusion does not adversely affect the mechanical properties of the irradiated polymer. Another method is to blend the polymer resin, powder or flakes with an antioxidant and subject it to ionizing radiation.
As mentioned above, when the radiation cross-linking is carried out in the presence of the antioxidant higher radiation dose levels need to be utilized to achieve the desired level of reduction in wear; however at higher radiation dose levels the antioxidant monotonically loses its potency as well, compromising the long-term oxidative stability of the polymer. Early studies with accelerated aging of antioxidant-containing polymers (0.1 wt % and 0.3 wt % vitamin-E/UHMWPE blend irradiated to 100 kGy and aged in a pressure vessel at 80° C. in oxygen for 2 weeks; see Oral et al. Biomaterials 2005 26(33):6657-6663) showed the oxidative stability of the polymer to be unaffected. We have discovered that when these irradiated polymers are stored (for example, stored on the shelf at room temperature) for a several months, they start showing signs of oxidation. Therefore, there is a potential for oxidative instability for irradiated antioxidant-containing polymers. This was an unexpected outcome as the accelerated aging methods were largely accepted to indicate long-term real aging behavior of UHMWPE. Nevertheless, accelerated aging data does not necessarily correlate or replicate real aging experience.
The addition of certain antioxidants into certain polymers inhibits the ability of the polymer to cross-link when subjected to ionizing radiation. Cross-linking typically takes place by the recombination reaction of two free radicals. Certain antioxidants, such as vitamin-E, could inhibit this recombination reaction through a number of possible mechanisms. This reduction in cross-linking efficiency of polymers containing antioxidants requires higher radiation dose levels to achieve the same cross-link density as that of radiation cross-linked virgin polymer (without antioxidant). At higher radiation dose levels, the activity of the antioxidant is reduced in favor for the increased cross-linking efficiency of the host polymer. However, the reduction in the antioxidant activity could compromise the oxidative stability of the host polymer. Therefore, new and alternative methods and approaches are desirable to achieve a desired cross-link density while minimizing the loss of activity of the antioxidant.
This application describes methods not found in the field for making antioxidant-doped, cross-linked polymeric materials having oxidative stability, for example, antioxidant-doped cross-linked ultra-high molecular weight polyethylene (UHMWPE), by post-irradiation heat treatment (such as annealing) of the antioxidant-containing UHMWPE, and materials used therein.